Reovirus, when used in combination with low levels of chemotherapy, mediates excellent immunotherapy of murine tumors and renders cured animals completely resistant to lethal challenge with homologous tumor. In vitro treatment of tumor cells with reovirus results in rejection of the treated cells when injected into syngeneic hosts. Preliminary studies in this laboratory indicate that noninfectious reovirus is as effective in tumor therapy as infectious virus. The aim of the proposed research will be to characterize the therapeutic effectiveness of noninfectious reovirus particles and determine the therapeutic necessity for virion-cell surface interaction. The degree of therapy induced by nonadsorbing core, antibody-neutralized and trypsin-modified reovirus types 1 and 3 will be compared to that mediated by adsorbing but noninfectious top component and UV- inactivated virions. The rejection of tumor cells treated in vitro with these noninfectious particles will also be determined. The virion attachment protein, delta 1, will be isolated and purified from reovirions and tested in vitro and in vivo for its ability to induce recognition and rejection of tumor cells. Finally, membranes isolated from tumor cells treated with infectious and noninfectious reovirus and delta 1 protein will be used to immunize animals to lethal tumor challenge. The ubiquitous host and tissue specificity and low pathogenicity of reovirus suggest significant potential for its use in the therapy of neoplasia in lower animals and humans. The possibility of using noninfectious virus or single virion polypeptides in tumor immunotherapy provides a most intriguing and promising approach to cancer treatment and to the study of the mechanisms of immune recognition and rejection of tumor cells.